Sacituzumab govitecan initial dose reduction in Polish patients with metastatic triple-negative breast cancer: Impact on efficacy and safety.

Abstract

e13136 Background: Sacituzumab govitecan (SG) is approved for the treatment of metastatic triple-negative breast cancer in the ≥2 treatment line setting, with a standard dosage of 10 mg/kg IV on Days 1 and 8 of a 21-day cycle. Clinical trials have demonstrated superior efficacy with the 10 mg/kg dose (vs 8 mg/kg), with a manageable safety profile. In clinical practice, initial dose reductions may occur despite the absence of formal guidelines, often as a precautionary measure. Furthermore, the fixed 200 mg vial size presents financial constraints within the Polish reimbursement system, as unutilized drug waste is not accounted for, inadvertently leading to initial dose modifications. Methods: This retrospective cohort study assessed the impact of initial SG dose reduction on clinical outcomes and tolerability in four oncology centers in Poland (August 2021–September 2024). Data from medical records included baseline characteristics, treatment details, survival outcomes, and adverse events (AEs) graded per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Survival was estimated using the Kaplan-Meier method, and intergroup differences were analyzed with the chi-square test. A multivariate Cox proportional hazards model evaluated the independent effect of dose reduction on overall survival (OS) and progression-free survival (PFS). A p-value < 0.05 was considered statistically significant. Results: Among 83 patients (median age: 55 years; interquartile range [IQR]: 30–86), with a median follow-up of 7.5 months (IQR: 3.22–11.29), the median PFS was 3.9 months (95% confidence interval [CI]: 2.77–4.55), and the median OS was 8.0 months (95% CI: 6.38–9.83). Grade ≥2 and ≥3 AEs were observed in 83.1% (n = 69) and 56.6% (n = 47) of patients, respectively. Granulocyte colony-stimulating factor (G-CSF) was administered in 84.3% (n = 70) of cases. Patients who received > 80% of the initial SG dose (n = 74) had significantly longer OS compared to those receiving ≤80% (n = 9) (median OS: 8.43 vs. 2.8 months, p < 0.001, hazard ratio [HR]: 4.826, 95% CI: 2.06–11.30), with no significant impact on PFS. Initial dose reduction did not significantly affect the toxicity profile (further dose reductions, Grade ≥2 or ≥3 AEs) or the need for G-CSF administration. Conclusions: In our study, initial SG dose reduction significantly affected OS but did not improve toxicity. Further research and reimbursement adjustments are needed to support appropriate dosing.